Pharmaceutical Validation

Friday, January 30, 2009

HVAC QUALIFICATION.

This HVAC Qualification, Design Qualification along with the attached Standard Operating Procedure, will, chapter by chapter take you through the task of raising a fully detailed DQ document. The main body is split into fourteen tables, each one probing the design requirements and standards for the individual requirement. Safety and security along with user operability are very detailed. The document will lead you through all these design aspects allowing you to delete some you feel are not important to your equipment. It is a superbly easy document to use and will ensure that you’re DQ’s are relevant, up to date and easy to execute. Practically all the requirements are in table form. Allowing fast and clearly presented results to be obtained.

HVAC QQUALIFICATION INSTALLATION.

This combined HVAC SOP and IQ template makes it so easy for you to raise a quality IQ. With the new suite of HVAC documents from the DQ - IQ - OQ - PQ, all user friendly and ready to go, your validation life has got much simpler. The final product is a professional and comprehensive Heating Ventilation and Air Conditioning Installation Qualification Protocol. One that you can produce in less than 60 minutes. Yes, think about it, we all know how long producing IQ documents has taken in the past. There is now no reason for not being able to produce 4 to 8, IQ protocols per 8 hour day, or a complete suite in one day.

GO TO STORE AND DOWNLOAD THESE DOCUMENTS NOW.

HVAC OPERATIONAL QUALIFICATION.

This easy to use HVAC Operational Qualification SOP and Protocol, can be simply and quickly converted (using find replace techniques) into your own company bespoke document. Now you can purchase these document in a suite DQ to PQ, getting you ready at express speed to qualify a system. It has never been quicker or simpler.

HVAC PERFORMANCE QUALIFICATION.

This fully formatted HVAC Performance Qualification is the last in the chain of qualifying tests that HVAC systems are subjected to, before being considered qualified. However environmental qualification is required to verify air quality.

STEAM QUALITY TESTING.

Steam Quality.
A continuous supply of saturated steam is required for steam sterilization and for humidification in certain EO sterilizers. Too high a level of non condensible gases will prevent the attainment of sterilization; too little moisture carried in suspension may allow the steam to become superheated during expansion into the chamber, while excess moisture may cause damp loads. Where steam systems are either routinely or irregularly shut down, large quantities of air will be present in the distribution system on restarting. It is recommended that in such circumstances a comprehensive and validated venting procedure should be applied and testing for steam quality is appropriate.

Non-condensible gases

Non-condensible gases result from the water from which the steam is generated. These gases will usually be air, though carbon dioxide may be present, caused by certain water treatment processes, typically water softeners. This is exacerbated by excessive aeration that can exist in many pharmaceutical water treatment plants where water is constantly recirculated and sprayed into the top of storage vessels. The effect of such gases being present in the steam supply to a sterilizer can be the same as air, none sterilization of the volume they occupy.

Superheated steam.

Superheated steam is steam at a temperature above its boiling point for its pressure. Superheated steam is a clear colour-less gas that will not condense until its temperature drops to its boiling point. Until this occurs the moisture necessary for sterilization cannot be produced and therefore presents a risk to the process. Superheated steam acts as hot air and requires sustained high temperatures and long hold times before sterilization can occur.

Dryness Value Test.

Wet steam is undesirable as it has less energy than dry steam and more importantly can cause wet loads. The packaging used for sterile products prevents reinfection when dry, but its bacterial retentive properties will be adversely affected by the presence of moisture. Wet loads can be considered to be un-sterile. The dryness fraction describes how dry steam is, with a value of 1 representing steam that is 100% dry, and therefore free of entrained moisture. Steam with a dryness fraction of 0.99 consists of 99% steam and 1% water. If we measure the latent heat present in steam that has a dryness fraction of 0.99 we will find that it possesses 99% of the full quotient of latent heat.

Bring Pure Steam Testing In House.

The draw back to carrying out steam quality testing has always been the lack of the correct Pitot and Expansion Tubes, along with difficulty of generating a quality protocol for qualification purposes. Now these excuses are gone, a quantity of the tubes have been manufactured to a tried and tested design, and are now in stock. The Pure Steam Quality protocol is also available for direct download. This document is not a template, it is a finished document. There is a prefixed SOP which will auto populate the document for you, with your company’s names and addresses, other than that the document is ready to execute.

VALIDATION RISK ASSESSMENT ASSESSMENT RATIONALE

The question - how much validation - has been an open subject for many years. Numerous companies brought in validation consultants, and or regulatory compliance experts, to guide them through these problems, but every so often, there would be clashes, or at least variations in opinion, in what the appropriate scope and depth of validation was. It was accepted by the regulators that there was going to be equipment used, that full validation was inappropriate for, yet the design or misuse of that piece of equipment, could be critical to product quality. This cannot be acceptable, so how do we prevent it occurring?

When we move away from these simple devices, to the average type of production equipment, here we find a range of equipment varying from purely mechanical (but intricate) equipment, to mechanical equipment assisted and or monitored and or managed by some degree of electronics. Then at the very pinnacle of validation we have the mainly electronic systems running extremely complex sophisticated software programs. All these systems play a major role in the product manufacturing process, they all require thorough validation using the existing framework of IQ – OQ - PQ, but they do not all require the same level of validation. How do we define the appropriate level?

First we have to look at validation and how the level of validation can be varied independently of the scope. If we list all the tasks we consider essential to complex software driven equipment validation, then drop off the tasks we consider inappropriate to the next level of equipment complexity, and so on. We appear to have four levels, with a significant step change between each of them.

Mechanical/electronic/electrical/full life cycle software, validation.
Mechanical/electronic/electrical/software, validation.
Mechanical/electronic/electrical/software, calibration.
None

The requirement for 21 CFR Part 11 compliance, can occur at all three of the upper levels of validation and so is addressed in the Validation Risk Assessment protocol as a separate requirement. To find that a piece of laboratory equipment requires the same degree of validation as a Distributive Control System may be disquieting, however any equipment that uses software alone, to automatically derive whether the product passes, or fails to pass, an inspection stage, must be subjected to FLCV. The laboratory equipment may have one such stage, the DCS will have many, however, one or many, the software lineage for each system, must follow similar methodologies.

Our Validation Risk Assessment (VRA) takes you through this assessment process and enables you to make a documented and justified decision as to the level of validation each piece of equipment will receive. This fulfils your obligation to ensure that all software is assessed, as to FLCV applicability.

Temperature Mapping Autoclave and Others

Positioning of the thermocouples in any temperature mapping exercise is down to judgment. A judgment that must be documented and justified.

In the case of an autoclave, heat is added in the form of pressurized wet steam, anything that can affect the distribution of the incoming steam, can affect uniformity of temperature. Conversely anything that can take heat away from the chamber can affect temperature uniformity.

Lets me say in this VALIDATION ONLINE BLOG, this stage if you want to be pedantic and put tc’s down the drain, the mapping exercise will probable fail. However you are there to verify that product will be sterilized, and product is never placed in the drain. Only the designated product containment area has to be verified.

If this is new installation then get hold of the FAT. In the FAT the chamber is subjected to detailed temperature transfer studies.

Even distribution of the in coming steam can be verified by placing a thermocouple sensor (tc) in each corner of the autoclave (8 tc’s).

Cooling due to heat loss will be maximum the further away you are from the steam inlet and the closer you are to metal that will conduct heat out of the chamber. That is usually, the door, or doors if double sided. If not double sided, then the end wall, and last but not least, the drain. The drain is a big source of heat loss. A tc should be placed as close to the drain, as product would be when the autoclave is in normal use. This gives us an additional 3 tc’s, bringing the total for a standard sized autoclave to 11 tc’s.

I have always considered this sufficient for 1.5 to 2.5 m3 autoclaves. Any bigger and I would concentrate on heat loses i.e. add tc’s to the top and bottom of the doors and or end wall.

It is most important to understand that it is impossible to validate an autoclave while using none validated steam.Your steam must be validated for – superheat – dryness – none condensable gases.

Make certain you do a pre and post mapping calibration, using instrumentation traceable to national standards.Happy mapping.

Do You Have to re-validate a computer, just because you have relocated it?

If you have a piece of equipment that your risk assessment has decided requires validation in accordance with cGMP requirements. It is mandatory that if that validation status is altered in any way, then the equipment must be revalidated. You cannot pick and choose, you must follow through the requirements of your own risk assessment. However you can use this risk assessment to set the scope of validation required.

Anyone who thinks they can move computer equipment around with no regard to the new location, is a person of very limited experience and little or no engineering knowledge. Radio Frequency Interference (RFI) is a serious problem in industry, and all validated equipment installations must be verified as immune to RFI, emitted from other equipment, that may be used in the installation area (electric motors – intermittent electric supplies - mobile phones - hand held radio’s used by security/maintenance/contractors - local transmitters taxis/police/firemen).

This is a mandatory requirement.

Out of literally hundreds of cases, here are just two, for this Validation Online Blog;
On the final tests at Sizewell B nuclear power station, we found that as soon as you keyed one of the maintenance hand-held UHF radios, the carrier signal switched the main emergency battery bank to maximum charge, and tried to cook them. When all else has failed this battery bank is there solely, to close down the reactor safely. The charging system controls had to be completely redesigned.

Two years ago we attended Jesus College in Cambridge regarding data corruption in one of the labs. This corruption had been investigated by literally dozens of electrical companies. After listening to the history we decided to install electrical supply and gauss monitors throughout the lab. After a week the records were analysed – everyone was stunned by the findings. We went on to analyse all the rooms that were in use, then marked-up the building drawings and the room doors as to their suitability for computer use. 15% of the rooms were condemned. The regulators are well aware of these problems, subsequently, they do expect RFI studies to have been carried out on all validated electronic equipment installations, and this is not the only requirement they expect.